Which Molecular Pathways Underlie Psychiatric Diseases?
Despite contributing significantly towards global disease burden, many psychiatric diseases are little understood. Our current understanding of mental health disorders has in a large part developed from observable abnormalities in behaviour and self-reported experiences, the latter being the primary means through which diagnosis occurs. Though useful, this is not ideal; not only due to subjectivity, but also as individuals suffering from these diseases frequently experience social difficulty, and a great deal of stigma is still associated with such disorders, which can provide a barrier to help seeking and lead to disparities in the quality of healthcare. Two troubling examples, highlighted by Pete Etchells, include evidence that after a diabetic emergency those with anxiety or depression are less likely to be hospitalised, and a report that women with mental health disorders are a third less likely to receive a mammogram.
Consequently, it is worth emphasising that psychiatric disorders are not simply “diseases of the mind”; with significant evidence for heritability, it is clear that they are underpinned by the disruption of biochemical processes, the cause of which may or may not have a genetic component. Furthering our understanding of the genetics of psychiatric disorders would clarify the biochemistry of these diseases, which could improve treatment, diagnosis, and stigma.
A recent study has carried out a genome wide association study (GWAS) to probe how genetics may influence mental health. GWAS cross-examines common genetic variation against disease incidence, for a great number of individuals, identifying whether any genetic variants occur more frequently in individuals with a certain disease: genes containing such variants are likely associated with the disease. The power of GWAS comes from the fact that genetic variants across the whole genome are investigated, rather than only a few genetic regions, as in more traditional methods, though GWAS is limited by the fact that it cannot by itself discern which genes (if any) are causal.
In the aforementioned study, the authors employ GWAS to identify any common pathways between bipolar disorder, depression, and schizophrenia. Histone methylation, which is involved in regulating gene expression, was found to be strongly associated with these psychiatric disorders, as was immune and neuronal signalling pathways. This suggests that there may be a genetic component underlying vulnerability to environmental risks, and also highlights overlap in the molecular pathways of these disorders. This approach could greatly assist in drug discovery, as pathways make much better targets than individual genes.
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